Deep vein thrombosis (DVT) and superficial vein thrombosis (SWT) associated primarily but not exclusively with medium and long duration aviation travel, is becoming an increasing concern both to passengers and to airlines. For clarity and to prevent repetition, DWT described in this document refers to a pathological thrombotic event in the lower limb and may be taken to include the various presentations within the deep, superficial and communicating venous vessels of the lower limb.
DVT is a thrombosis that forms in the deep vein system of the lower leg, usually between the ankle and the upper calf. It is a common condition in patients receiving medical or surgical treatment in hospital. The condition is serious, potentially fatal, and very difficult to diagnose by external examination. The clot formation may develop very rapidly, detach from the wall of the vein and move through the blood stream before a problem is recognised. The clot may travel through the veins and lodge in essential organs such as the heart, brain or lungs, resulting in life-threatening conditions such as stroke, pulmonary embolism and myocardial infarction. The annual incidence of DVT in USA and Europe is approximately 160 per 100,000 and the rate of fatal PE is 50 per 100,000. Various studies have shown that about one third of patients undergoing major surgery without sufficient prophylaxis will develop DVT. In addition perioperative death due to pulmonary embolism has been shown to occur in 0.5% to 3.4% of patients undergoing major surgery.
The formation of a clot within the vein lumen is the result of interplay of various factors. The underlying pathophysiology suggests that three main factors are responsible for the development of thrombosis in the peripheral veins. This is termed as “Virchow's triad”: i) damage to the vein wall (endothelium); ii) stasis of venous blood (slowing of blood flow); iii) a change in the constitution of the blood (i.e. increased coagulability). Since Virchow, other factors have been identified, but this theory is still accepted. Thrombi usually form in areas of slow or disturbed flow in large venous sinuses and in the valve pockets. The majority of thrombi originate in the soleal veins and valve pockets following surgery. Thrombi also form in vein segments, which have been subjected to direct trauma. A principal feature of clot formation relating to DVT is the pooling of stationary blood in the lower leg, as a result of staying immobile for too long, commonly with the leg in a dependant position. However, DVT may occur in lower limbs while lying supine, frequently where there are additional risk factors such as injury, inflammation or post surgery.
To understand the physiological processes responsible for DVT, it is first essential to describe the normal venous blood return of the lower limb.
During recumbency, (when a subject is lying down with the legs and the heart at the same level), blood flows evenly along the superficial and deep veins towards the heart, propelled by a relatively small force coming through the capillaries. This is known a ‘vis-a-tergo’ (force from behind) and is the residual force generated by the heart and transmitted through the microvascular bed to the veins.
However, during standing the highly efficient calf pump is the main mechanism of venous return. During motionless standing the veins are full with a pressure equal to the hydrostatic pressure of a column of blood extending from the point of measurement up to the level of the heart. The hydrostatic pressure at the ankle is approximately 90 mmHg. Venous return is aided by the ‘vis-a-tergo’ of the capillary bed, also by respiratory movements, particularly inspiration. The close proximity of arteries to veins also aids venous return, as pulsations of adjacent arteries may assist flow in veins with competent valves. Although these mechanisms aid venous return, long standing high venous pressures can result in oedema formation even in normal limbs.
The musculovenous pumps of the lower limb and the presence of competent venous valves play an important role in aiding venous return and decreasing venous pressure in the lower limb. There are three pumps: the foot pump, calf pump and thigh pump.
The venous foot pump assists in venous return from the lower limbs as follows. Weight bearing causes flattening of the plantar arch and stretching and narrowing of the plantar veins expelling blood upwards from the foot towards the calf segment.
The calf pump is the most efficient and the most powerful of the three pumps, and during exercise it becomes the principal mechanism of venous return. During rhythmic exercise such as walking, it decreases the volume of blood in the capacity vessels of the lower limb and thus more blood is available for redistribution to other regions such as the pulmonary vascular bed. During muscle contraction, blood is ejected from the calf veins and into the thigh where it is picked up by the thigh muscle pump. Competent valves prevent reflux of blood back into distal veins.
As a result of muscle pump contraction during walking, the venous pressure at the ankle (measured from the Long Saphenous Vein) is reduced from 90 mmHg down to approximately 25 mmHg in the normal limb. The effectiveness of the venous muscle pump is judged by its ability to decrease venous pressure, and in normal limbs venous pressure is reduced well below hydrostatic levels. By lowering the venous pressure, the calf pump reduces oedema formation, which would occur as a result of high pressures in the upright position. The muscle pump action together with competent valves thus reduces venous pressure and prevents oedema formation. The fall in venous pressure during exercise, results in an increase in the arteriovenous pressure gradient by nearly 50%. The calf muscle pump has been termed the ‘peripheral heart’. The increased arteriovenous pressure gradient results in increased perfusion pressure in the distal tissues and increased perfusion. Thus it not only decreases venous pressure but also increases blood flow.
Anatomic Arrangement: The conventional view of the muscle pump is based on the concept that the deep veins are compressed by contracting muscle and the superficial veins drain into the deep veins. The anatomic arrangement of the deep veins and their valves, set within and between the muscles of the limb, constitute a reciprocating pump mechanism. The arrangement is described as parallel reciprocating pumps (that empty reciprocally) that are linked in series extending along the length of the limb. The input from each pump comes from the deep vein below and from the superficial vein in the corresponding segment via the perforating veins. The blood is expelled towards the heart and competent valves are required to prevent retrograde flow from upstream veins.
In the lower leg, the deep veins are either intramuscular (the soleal sinuses and gastrocnemial veins) or intermuscular (the posterior and anterior tibial and peroneal veins). The soleal veins are large, thin walled, valveless sinuses, which act as pump chambers. The soleal sinusoids constitute the main collecting chambers of the calf muscle pump. The calf muscles are enclosed by a dense, inelastic covering (deep fascia). This tight fascial investment permits generation of high pressures within the muscle during contraction. This pressure is exerted on the muscle veins especially the soleal sinusoids and results in forceful expulsion of blood within them towards the heart.
Pathophysiology and calf pump failure: The normal functioning of the calf muscle pump depends on the integrity of the venous valves, patency of the deep veins, activity and strength of the muscles and mobility of the ankle and knee joints. Calf pump failure occurs as a result of the following:
Incompetent venous valves. The venous valves play an important role in calf pump function as they prevent retrograde flow of blood as the musculo-venous pumps propel blood from the lower leg towards the heart. Valve failure can occur in the superficial veins, which results in the development of varicose veins, or it can occur in the deep veins. Deep venous incompetence can occur as result of valve destruction following an episode of deep vein thrombosis or it can have a primary cause. As a result of this retrograde flow, especially in the deep veins, the calf pump is rendered ineffective and fails to effectively reduce venous pressures during exercise. This causes venous hypertension which can lead to skin changes and ulceration.
Obstruction of the deep veins: If the deep veins above the knee (Femoral, Popliteal, Iliac) are obstructed by thrombus following an episode of DVT, calf muscle pump function is affected as blood is ejected into vessels with reduced patency.
Muscle weakness/atrophy: The activity and strength of the muscle declines with ageing and as the strength of the muscle decreases so does the effectiveness of the calf pump.
Immobility of the ankle or knee joint: This also has an effect on calf pump function.
In summary, under normal conditions, blood in the veins of the lower leg is pumped by the action of the calf muscles, not by the heart. In a stationary, seated position, this normal physiological action is significantly reduced or absent.
DVT can strike any traveller, regardless of physical condition, age, or gender. A commonly held perception is that the condition is only related to long-haul journeys, this is not the case as DVT may present as a result of even short-term travel. Everyone who is inactive in a leg-cramped position for several hours is at risk. DVT is also not confined to those flying economy class. First-class passengers are also at risk, as are long distance auto and rail travellers. London's Heathrow Airport records one passenger death per month from DVT. One nearby hospital recorded thirty passenger deaths from DVT in a three-year period. DVT is the fourth leading cause of strokes in the United States. Approximately 2,000 Americans died from travel-related DVI-induced strokes in 2003.
Circumstances other than travel can also lead to DVT risks; for example, immobile patients in care homes, patients immobile during and post surgery, during prolonged bed rest, and patients with lower limb paralysis.
Risk factors for DVT have been identified which allow clinical stratification of patients into low, moderate and high-risk groups. Risk assessment depends on ‘patient factors’ and ‘operation factors’. The ‘patient factors’ which signify a greater than average risk of DVI are: age >40 years, trauma, cancer, re-operation, infection, oestrogen therapy, obesity, renal transplantees, previous DVT or PE, established hypercoagulable states, neurological disorders, or varicose veins. In addition, surgery to the lower limb, particularly the hip and knee, gynaecological procedures, abdominal surgery and neurosurgery all carry a risk of DVT ranging from 14% in gynaecological surgery to approximately 50% in hip and knee replacement surgery. The methods available today for the prevention of DVT are pharmacological methods, which mainly reduce blood coagulability, and mechanical methods, which increase the rate of venous blood flow.
Mechanical methods of DVT prophylaxis include the use of graduated compression stockings; intermittent pneumatic compression, as well as foot impulse technology. Out of these methods, graduated compression stockings are the most widely accepted. Compression stockings have the advantage that they can be used during recumbency as well as during sitting, standing and walking.
Elastic compression stockings for DVT prophylaxis are graduated with pressures of 18 mmHg at the ankle, gradually reducing along the length of the leg (14 mmHg at the calf and 8 mmHg at the upper thigh). This pressure is sufficient to produce venous compression and an increased velocity of blood flow when the patient is supine, without affecting arterial inflow. The stockings are designed so that the tops do not become constriction bands around the thigh.
Elastic compression stockings have been shown to reduce venous dilatation as they reduce diameter and hence venous volume. They also cause an increase in venous flow velocity (blood flow velocity will increase as a result of narrowing of the venous diameter when the arterial inflow remains unchanged). Using Doppler ultrasound, it was shown that elastic stockings increase femoral vein blood flow velocity and the effect persists for up to 30 minutes after stocking removal. The increased venous flow velocity and decreased venous pooling, i.e. reduction of stasis may reduce the occurrence of venous thrombosis. However, stockings in the immobile patient do not facilitate muscle pump function in the lower limb.
Used alone, clinically appropriate use of stockings reduces the incidence of postoperative DVT by approximately 60% and when in combination with other preventative methods such as low dose heparin or intermittent pneumatic compression use of stockings may reduce the incidence by up to 85%. Stockings are also effective in reducing oedema.
Elastic compression is contraindicated in the presence of peripheral arterial disease. Stockings are often incorrectly fitted, or the wrong size and as a result the required compression gradients are not achieved. They can be uncomfortable to wear which causes poor patient compliance, they can also slip down the leg, and they are often difficult to apply (especially for the elderly). They can also cause superficial thrombophlebitis. Stockings must also be replaced every six months as frequent washing and wearing causes a loss of elasticity.
Intermittent pneumatic compression (IPC) has been commonly used in DVT prophylaxis. It can either be a single chamber device applying uniform compression to the whole limb, or it could exist as sequential chambers applying pressure in sequential fashion from the foot to the thigh (sequential compression device—SCD). Most commercially available SCD devices have a fixed cycle time of compression and deflation. More recently, new devices have been introduced which can detect changes in venous volume and respond by initiating the next compression cycle when the veins are considerably full. IPC can also be applied to the foot alone as a ‘foot pump’ (foot impulse technology). IPC is thought to work by increasing the rate of venous flow through the deep veins thus preventing stasis, which may lead to deep vein thrombosis. It has been shown to be more effective in DVT prophylaxis when used in combination with graduated compression stockings than on its own. IPC has been shown to enhance venous emptying of the limb and reduce oedema. It has also been suggested that external compression acts by encouraging the release of fibrinolytic activators from the venous endothelium and improve tissue fibrinolysis.
Arterial flow can be increased with intermittent compression. Intermittent pressure waves with pressure peaks at the systolic ankle pressure have been shown to increase blood flow in the large arteries and in the skin.
Limitations of intermittent pneumatic compression devices: These devices are often bulky and not portable and cannot be used when the patient is mobile. External pneumatic compression devices can also cause arterial ischemia. It must be also applied cautiously in patients with severe heart failure as it may result in a shift of the blood volume centrally.
There are a number of current strategies for prevention of travel-related DVT, which however are unsatisfactory for a number of reasons.
Exercise is primarily recommended, as activity of the lower limb, which will stimulate blood flow. Many airlines advocate an in-flight exercise programme, with particular attention to exercising the calf muscles. Observance of these programmes is generally poor and sporadic, thereby greatly reducing the value of this therapy. Additionally, there is no method for assessing passenger compliance, which may be of value from a legal standpoint. Furthermore, active movement throughout the cabin area is actively discouraged during turbulence and in general in response to the heightened terrorist threat.
Some practitioners suggest an Aspirin tablet before travelling, and at intervals during the trip, as an anti-coagulant. Most healthy people, however, are reluctant to take drugs as a purely speculative preventative measure. Furthermore, such an intervention should only be recommended by a medical healthcare professional who is familiar with the individual's medical history, as there are a number of significant risks associated with the use of aspirin. Again, there is no method for assessing compliance from a legal perspective.
Graduated compression stockings and socks have been provided by some airlines, or are available for purchase over the counter. These stockings are designed to exert a degree of compression at the ankle, with pressure gradually decreasing up the length of the hosiery. This action forces surface veins' blood into the deep vein system of the legs thereby supposedly correcting weak blood flow. Commercially available below knee graduated compression stockings tend to have a maximum compression at the ankle of 10-30 mmHg. This approach suffers from a number of problems, including the random nature of the applied pressure pattern each time the stocking is applied. Some commercial flight socks suggest they apply a pressure approximating 10 mmHg, which would appear to be of reduced value compared with the interface pressures advocated medically for surgical stockings.
Effective compression may not be achieved with a standardised sock shape, due to the highly variable shape of the lower limb. Moreover, the applied conditions are static, the foot, calf and thigh pumps inoperative, and therefore compression stockings may only offer limited reduction in DVT risk. The useful lifespan of such products is related directly to usage and care, with any proportional benefits decreasing rapidly with repeated usage. Finally, wearing of compression garments can be uncomfortable, and this alone may lead to reduced compliance.
A range of strategies exists for prevention of DVT in a clinical environment, which are unsatisfactory for a number of reasons.
For certain situations, in particular operating theatres, a variety of inflatable devices have been used to prevent DVT in the form of inflatable boots applied to each leg. As air is pumped into the boot, the leg is squeezed, forcing out the blood. These devices require pumps, and are rather obtrusive and cumbersome for use outside the operating theatre. Such systems are uncomfortable for the conscious patient and grossly inhibit any independent mobility when applied.
Devices and methods for electrical stimulation of leg muscles to reduce the risk of DVT are known. U.S. Pat. No. 5,674,262 describes a device which provides electrical stimulation of the calf muscle, together with a compression device used to compress the foot. U.S. Pat. No. 6,393,328 describes a multi functional electrical stimulation device which may be used to stimulate a variety of muscles, not only leg muscles. WO99/53996 describes a device which stimulates muscle twitch of the calf muscle, with the aim of reducing DVT. WO99/64105 describes a device for electrical stimulation of the calf muscle; the device incorporates a motion sensor for providing feedback to control the stimulation signal based on muscle contraction. DE 39 16 994 A1 describes a device having a longitudinal arrangement of several electrodes to provide stimulation along the length of the leg. WO03/063960 describes a device having electrodes integrated into a bandage housing which may be used to electrically stimulate the leg of a patient.
Prior art devices and methods have a number of shortcomings. One such shortcoming is that the devices must either stimulate muscles with a low level of contraction, which may not be sufficiently effective in promoting circulation to reduce DVT; or they may use higher levels of contraction, which will cause the muscles to contract sufficiently to cause movement of the limb, which may be undesirable in certain situations, and which may be painful.
It is among the intentions of the present invention to provide an alternative treatment for avoidance or reduction of the risk of DVT, SVI, and/or other circulatory disorders in the lower limb. This is achieved, in part, in certain embodiments of the invention by the use of electrical stimulation of lower limb muscles to obtain isometric muscle contraction in order to promote blood circulation. By isometric muscle contraction is meant contraction of opposing groups of muscles, such that protagonistic and antagonistic muscles or muscle groups are stimulated such that no or very little movement of the limb is effected.
The present invention may be additionally applied to the prevention, management and treatment of a range of disorders related to the dysfunctions of lower limb blood flow, including but not limited to ischaemia, ulceration, oedema, or phlebitis. Other disorders, including osteoporosis, heart failure, heart disease, common and pulmonary hypertension, may be treated.